Stimulated Raman imaging for label-free histology to guide brain tumor surgery

用于无标记组织学的受激拉曼成像指导脑肿瘤手术

• 批准号: 9140064
• 负责人: Fake Lu
• 金额: $ 9.45万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-08 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9140064
• 关键词: Agar; Algorithms; Applications Grants; Area; Artificial Intelligence; Atypia; Award; Axon; Basic Science; Biological; Biological Markers; Biological Preservation; Biophotonics; Bone marrow biopsy; Brain; Brain Neoplasms; Cancerous; Cell Density; Cellular Morphology; Chromatin Structure; Clinical; Clinical Pathology; Clinical Research; Collagen; Computational algorithm; Computer Vision Systems; Computer software; Computers; Cryoultramicrotomy; Data; Decision Making; Devices; Diagnosis; Diagnostic; Documentation; Effectiveness; Evaluation; Excision; Fine-needle biopsy; Fluorescence; Frequencies; Fresh Tissue; Frozen Sections; Funding; Glioma; Goals; Gold; Health; Healthcare; Hematoxylin and Eosin Staining Method; Histology; Histopathology; Home environment; Hospitals; Image; Image Analysis; Imagery; Imaging Techniques; Injury; International; K-Series Research Career Programs; Knowledge; Label; Laboratories; Lead; Learning Skill; Life; Linear Algebra; Lipids; Machine Learning; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Medicine; Mentors; Methodology; Methods; Microscopy; Mitotic; Modality; Molecular; Morphologic artifacts; Morphology; Myelin Sheath; Necrosis; Neoplasm Metastasis; Nervous System Physiology; Neurologic Deficit; Neuronavigation; Neurosurgeon; Normal tissue morphology; Nuclear; Nucleic Acids; Online Systems; Operating Rooms; Operative Surgical Procedures; Optics; Outcome; Pathologic; Patient-Focused Outcomes; Patients; Pituitary Gland Adenoma; Postoperative Period; Preparation; Procedures; Process; Proteins; Quality of life; Raman Spectrum Analysis; Research; Research Infrastructure; Research Personnel; Residual Tumors; Resolution; Sampling; Series; Shapes; Signal Transduction; Solid; Specimen; Speed; Staining method; Stains; Structure; Surgical Injuries; Surgical Oncology; System; Technology; Time; Tissue Banking; Tissue Banks; Tissue Stains; Tissues; Training; Training and Education; Translational Research; Treatment Step; Tumor Biology; Tumor Tissue; Universities; Validation; Woman; Work; World Health Organization; Writing; Xenograft procedure; angiogenesis; base; bioimaging; brain tissue; brain tumor resection; cancer cell; cancer diagnosis; career; career development; catalyst; chemical bond; chemical group; clinical practice; clinically relevant; commercialization; computer science; disorder prevention; experience; frontier; gray matter; human disease; image guided; image guided therapy; imaging system; improved; innovation; instrument; meningioma; microscopic imaging; mouse model; neuropathology; neurosurgery; novel; novel strategies; operation; outcome forecast; peer; programs; prototype; screening; skills training; standard care; symposium; tool; tumor; white matter

 DESCRIPTION (provided by applicant): The goal of brain tumor surgery is to maximize removal of tumor without causing permanent neurologic deficits. Studies have shown that outcomes for patients depend strongly on these two variables. However, this is difficult because tumor tissue is often indistinguishable from healthy tissue in the operating room. Preoperative and intraoperative MRI through neuronavigation can be used to guide brain tumor surgery, but it is not able to accurately delineate the tumor margin due to the brain deformation and brain shift during surgery. H&E staining as the current gold standard is often performed intraoperatively for preliminary diagnosis, but it is not used to guide extent of resection routinely due to the limitations including tissue artifacts, labor-intensiveness, and time delay. Fluorescence guided surgery is beginning to be used to guided brain tumor surgery, but is generally not useful for low grade gliomas, the tumors which pose the greatest challenge and opportunity to extend survival and improve quality of life. Stimulated Raman imaging (SRI) has been used for rapid label-free biomolecular mapping in live tissue. Recently we have developed a novel approach with SRI to image nucleic acids, together with protein and lipids. Visualization of nucleic acids allows definition of nuclear morphology and chromatin structures, thereby enabling pathologic evaluation of clinically relevant cellular morphology, providing almost equivalent information to H&E staining. The goal of this translational research is to establish the methodology and practice for label-free histopathology with SRI for brain tumor diagnosis, and eventually develop it into a clinical device for ambient SR imaging of fresh tissue in the operating room in real time If the aims are achieved, this project will greatly improve the current clinical practice of brain tumor surgery by providing real time tissue diagnosis for more precise control of the extent of resection and preservation of neurologic function. Furthermore, this approach may be of value for all oncologic surgeries and other clinical pathology such as fine needle biopsies and bone marrow biopsy. The candidate for this award Dr. Fake Lu is a postdoctoral research fellow at Brigham and Women's Hospital. Dr. Lu has extensive experience and expertise in biophotonics and biomedical optics, specialized in system innovations of stimulated Raman microscopy and multiphoton microscopy for biomedical applications. BWH is an international leader in basic, clinical and translational research on human diseases, and has established multiple research programs to promote the work and professional career development of young investigators. BWH is also home to the National Center for Image Guided Therapy (P41) and the Advanced Multi-modality Image Guided operating suite (AMIGO) infrastructure which will greatly support to proposed research. Dr. Lu's long term research goal is to develop and apply advanced biophysical and optical technologies and devices to improve understanding, diagnosis, treatment, and prevention of diseases, such as cancers, for better health care. His long-term career goal is to become an independent investigator working at the frontier of translational research. The immediate objectives for the five-year award period is to 1) establish and evaluate label-free histopathology SRI for brain tumor diagnosis, 2) to demonstrate ambient imaging of surgically removed fresh tissue for diagnosis of brain tumors for real time guidance of neurosurgical resection, 3) to develop a novel stimulated Raman microscopy to collect full spectral data in parallel for label-free histopathology, as well as lipid biomarker screening, 4) t develop a computer algorithm for SR image analysis to realize automatic brain tumor diagnosis, and 5) finally by integrating the instrument and software to build and demonstrate a prototype of a clinical device for guiding neurosurgical resection of brain tumors. This device could also be used for other oncologic surgeries and will have great potential for commercialization. To conduct the proposed research, in addition to further develop his current strengths in biophotonics, stimulated Raman microscopy, and nonlinear optical microscopy, Dr. Lu plans to receive more education and training to enrich and expand his knowledge and expertise in the following four areas: 1) to receive critical training in conducting translational research, 2) to enrich his knowledge and deepen his understanding in brain tumor biology and medicine, 3) to learn skills in developing computer algorithms for SR image analysis, and 4) to prepare for writing grant applications and seeking funding independently. Dr. Lu will participate in 12 formal courses selected from those offered by Harvard Catalyst and Cold Spring Harbor Laboratory. He will attend weekly seminars at BWH and Harvard University, seminar series on biomedical image analysis organized by MIT Computer Science and Artificial Intelligence Laboratory. He will also attend one or two annual conferences per year to present his work for peer discussion. A strong mentoring team was organized to provide solid support to the proposed research and Dr. Lu's career development, including Dr. Alexandra Golby in neurosurgery at BWH, Prof. X. Sunney Xie in coherent Raman microscopy at Harvard, Prof. Nathalie Agar in molecular cancer diagnosis at BWH, Prof. Polina Golland in computer-based image analysis at MIT, and Dr. Sandro Santagata in neuropathology at BWH. This career development award will provide Dr. Lu with the training and skills needed to transition into an independent investigator in translational research.

 描述（由适用提供）：脑肿瘤手术的目的是最大程度地切除肿瘤而不会引起永久性神经系统缺陷。研究表明，患者的结果在很大程度上取决于这两个变量。但是，这很困难，因为肿瘤组织通常与手术室健康组织没有区别。术前和术中MRI通过神经训练可用于指导脑肿瘤手术，但它是H＆E染色，因为当前的黄金标准通常用于术中用于初步诊断，但由于通常用于指导切除范围，因为限制限制，包括组织工子，劳动力型，劳动力型，劳动力延迟和时间延迟。荧光引导手术开始用于引导脑肿瘤手术，但通常对低级神经胶质瘤没有用，这是扩大生存和改善生活质量的最大挑战和机会。刺激的拉曼成像（SRI）已用于活组织中的无标记生物分子映射。最近，我们开发了一种新型的SRI方法来对核酸进行成像，以及蛋白质和脂质。核酸的可视化允许定义核形态和染色质结构，从而对临床相关的细胞形态进行病理评估，从而为H＆E提供了与H＆E染色几乎等效的信息。这项翻译研究的目的是建立用于脑肿瘤诊断的无标签组织病理学的方法和实践，并最终将其开发为临床手段，以实现目标的环境SR成像，如果实现了目标，则可以通过提供实际的脑肿瘤手术诊断的范围和确定性范围，以改善该项目的当前项目，以改善该项目的当前临床诊断，以确定实际组织诊断的范围。此外，这种方法对于所有肿瘤学手术和其他临床病理（例如细针活检和骨髓活检）可能具有价值。该奖项的候选人假Lu博士是Brigham and妇女医院的博士后研究员。 Lu博士在生物素和生物医学光学方面具有丰富的经验和专业知识，专门研究刺激的拉曼显微镜和多光显微镜的系统创新，用于生物医学应用。 BWH是基本，临床和翻译人类疾病研究的国际领导者，并建立了多个研究计划，以促进年轻研究者的工作和职业发展。 BWH还是国家图像指导疗法中心（P41）和先进的多模式图像指导操作套件（Amigo）基础设施的所在地，该基础设施将极大地支持拟议的研究。 Lu博士的长期研究目标是开发和应用先进的生物物理和光学技术和设备，以改善对疾病（例如癌症）的理解，诊断，治疗和预防，以改善医疗保健。他的长期职业目标是成为翻译研究前沿工作的独立研究者。 The immediate objectives for the five-year award period is to 1) Establish and evaluate label-free histopathology SRI for brain tumor diagnostics, 2) to demonstrate ambient imaging of surgically removed fresh tissue for brain tumors for real time guidance of neurosurgical resection, 3) to develop a novel stimulated Raman microscopy to collect full spectrum data in parallel for label-free histopathology, as well as lipid biomarker筛选，4）开发用于SR图像分析的计算机算法以实现自动脑肿瘤诊断，而5）最后，通过整合仪器和软件来构建和演示临床装置的原型，以指导脑肿瘤的神经外科切除术。该设备也可以用于其他肿瘤手术，并具有巨大的商业化潜力。为了进行拟议的研究，除了进一步发展他在生物素器方面的当前优势，刺激拉曼显微镜和非线性光学显微镜外，Lu博士计划接受更多的教育和培训，以在以下四个领域中丰富和扩展其知识和专业知识：1）接受对他的知识的重要培训，以便在脑海中进行培训，以发展其知识，并在脑海中发展，并在脑海中发展，并加深对脑海的了解，3）分析，以及4）准备编写赠款申请并独立寻求资金。 Lu博士将参加从哈佛大学催化剂和冷泉港实验室提供的12个正式课程。他将参加BWH和哈佛大学的每周开创性，由麻省理工学院计算机科学和人工智能实验室组织的生物医学图像分析开创性系列。他还将每年参加一两个年度会议，介绍他的工作进行同行讨论。 A strong mentaling team was organized to provide solid support to the proposed research and Dr. Lu's career development, including Dr. Alexandra Golby in neurosurgery at BWH, Prof. X. Sunney Xie in coherent Raman microscopy at Harvard, Prof. Nathalie Agar in molecular cancer diagnostic at BWH, Prof. Polina Golland in computer-based image analysis at MIT, and Dr. Sandro Santagata in neuropathology at BWH。该职业发展奖将为Lu博士提供过渡到转化研究独立研究者所需的培训和技能。